Kenjiro Tatematsu

Although cholesterol (Chol) is widely recognized as a risk factor for cardiovascular disease, dietary Chol intake has been reported to extend the lifespan of stroke-prone spontaneously hypertensive rats (SHRSP). The mechanisms responsible for this paradoxical effect remain unclear. The present study examined changes in organ lipid profiles and associated molecular factors in SHRSP rats fed a Chol-enriched diet. Four-week-old male SHRSP/Izm rats were assigned to three groups and fed ad libitum for 12 weeks with either a control diet (Ctr), a diet supplemented with 1% w/w Chol (Chol), or a diet containing 1% w/w Chol plus 0.025% w/w lovastatin to suppress endogenous Chol synthesis. Systolic blood pressure was measured before and after the feeding period, and tissues were collected for analyses of sterol content, fatty acid composition, prostaglandin E ₂ (PGE ₂ ) levels, and renal histopathology. Relative to the Ctr group, the Chol group exhibited a significant 9–10% reduction in systolic blood pressure. This reduction was accompanied by pronounced alterations in lipid profiles, including changes in phytosterol content and decreased arachidonic acid ratios in serum and kidney. There was a downward trend in hepatic PGE ₂ levels, and a similar tendency was observed in the kidney. Comparable changes in lipid profiles were observed in the Chol + lovastatin group. Histological analysis revealed modest attenuation of renal pathological features in Chol-fed rats. This study demonstrates for the first time that dietary Chol reduces renal phytosterol accumulation and suppresses the AA-PGE ₂ axis, changes that coincide with a 9–10% reduction in systolic blood pressure and attenuated glomerular inflammation. These integrated findings provide a mechanistic framework linking dietary Chol to the previously reported lifespan extension in this stroke-prone model. Although these changes may contribute to improved renal pathology, further studies are required to clarify causal relationships.

Although cholesterol (Chol) is widely recognized as a risk factor for cardiovascular disease, dietary Chol intake has been reported to extend the lifespan of stroke-prone spontaneously hypertensive rats (SHRSP). The mechanisms responsible for this paradoxical effect remain unclear. The present study examined changes in organ lipid profiles and associated molecular factors in SHRSP rats fed a Chol-enriched diet. Four-week-old male SHRSP/Izm rats were assigned to three groups and fed ad libitum for 12 weeks with either a control diet (Ctr), a diet supplemented with 1% w/w Chol (Chol), or a diet containing 1% w/w Chol plus 0.025% w/w lovastatin (Stt) to suppress endogenous Chol synthesis. Systolic blood pressure was measured before and after the feeding period, and tissues were collected for analyses of sterol content, fatty acid composition, prostaglandin E₂ (PGE ₂ ) levels, and renal histopathology. Relative to the Ctr group, the Chol group exhibited a significant 9–10% reduction in systolic blood pressure. This reduction was accompanied by pronounced alterations in lipid profiles, including changes in phytosterol content and decreased arachidonic acid ratios in serum and kidney. There was a downward trend in hepatic PGE ₂ levels, and a similar tendency was observed in the kidney. Comparable changes in lipid profiles were observed in the Stt group. Histological analysis revealed modest attenuation of renal pathological features in Chol-fed rats. This study demonstrates for the first time that dietary Chol reduces renal phytosterol accumulation and suppresses the AA-PGE₂ axis, changes that coincide with a 9–10% reduction in systolic blood pressure and attenuated glomerular inflammation. These integrated findings provide a mechanistic framework linking dietary Chol to the previously reported lifespan extension in this stroke-prone model. Although these changes may contribute to improved renal pathology, further studies are required to clarify causal relationships.

Feeding canola oil （Can） to stroke-prone spontaneously hypertensive rats （SHRSP） shortens their lifespan. This anomalous effect was also observed with partially hydrogenated oils the effectiveness of fully hydrogenated oil is still unclear. This study aimed to investigate the lifespan of SHRSP fed diets containing 10 %（w/w） of fully hydrogenated Can （FHCO） or other edible oils. For measuring survival, ｍale SHRSP were fed a test diet consisting of a mixture of rodent basal diet and one of the test oils in a 9:1 ratio. During the study period, food consumption of rats given FHCO was significantly increased（ 15–20% w/w） compared to the other oils. However, body weight gain in the FHCO group was suppressed and significantly less （10–12%） than that in control at 9–11 weeks of age. None of the rats in the FHCO group died until 180 days although other groups were died by around 130 days. Furthermore, after feeding test diets to other SHRSP for 7 or 12 weeks, blood pressure, serum lipid level, and histological analysis in brain and kidney were measured. FHCO remarkably decreased the serum cholesterol level both 7 and 12 weeks feeding and suppressed elevation of the systolic blood pressure from 12 weeks old. In addition, while some rats exhibited cerebral hemorrhage and renal dysfunction in the Can group at 16 weeks of age, no symptoms were observed in the FHCO group. This study suggested that complete hydrogenation decreases the toxicity of Can and even prolongs the lifespan in SHRSP.

Background: Canola oil (Can) and several vegetable oils shorten the lifespan of stroke-prone spontaneously hypertensive rats (SHRSP). Although similar lifespan shortening has been reported for partially hydrogenated Can, the efficacy of fully hydrogenated oils on the lifespan remains unknown. The present study aimed to investigate the lifespan of SHRSP fed diets containing 10 % (w/w) of fully hydrogenated Can (FHCO) or other oils. Methods: Survival test: Upon weaning, male SHRSP were fed a basal diet for rodents mixed with one of the test oils —i.e., FHCO, Can, lard (Lrd), and palm oil (Plm) throughout the experiment. The animals could freely access the diet and drinking water (water containing 1 % NaCl), and their body weight, food intake, and lifespan were recorded. Biochemical analysis test: Male SHRSP were fed a test diet with either FHCO, Can, or soybean oil (Soy) under the same condition, except to emphasize effects of fat, that no NaCl loading was applied. Soy was used as a fat source in the basal diet and was set the control group. Blood pressures was checked every 2 weeks, and serum fat levels and histological analyses of the brain and kidney were examined after 7 or 12 weeks of feeding. Results: During the survival study period, the food consumption of FHCO-fed rats significantly increased (15–20 % w/w) compared with that of rats fed any other oil. However, the body weight gain in the FHCO group was significantly less (10–12 %) than that in the control group at 9–11 weeks old. The FHCO (> 180 days) intervention had the greatest effect on lifespan, followed by the Lrd (115 ± 6 days), Plm (101 ± 2 days), and Can (94 ± 3 days) diets. FHCO remarkably decreased the serum cholesterol level compared with Can and the systolic blood pressure from 12 to 16 weeks of age. In addition, while some rats in the Can group exhibited brain hemorrhaging and renal dysfunction at 16 weeks old, no symptoms were observed in the FHCO group. Conclusion: This current study suggests that complete hydrogenation decreases the toxicity of Can and even prolongs the lifespan in SHRSP.

[Aim of the study] Canola oil (CAN) ingestion is known to shorten the life-span of male SHRSP and the life-shortening is preceded by a decrease in plasma testosterone and an increase in aldosterone. The present study was conducted to clarify the target of the toxicity. [Methods] Male SHRSP were given an AIN-93G diet containing 10w/w% soybean oil (Control) or CAN and tap water ad libitum for 8 weeks. At the 8th week the animals were sacrificed and plasma concentrations of testosterone, aldosterone, LH and FSH were measured using ELISA kits. Testes were isolated and histopathologically examined. Gene expressions for ACE and ACE2 in the lung, kidney and testis were measured. [Results and discussion] CAN-induced decrease in plasma testosterone and increase in aldosterone were confirmed. Both, plasma LH and FSH were similar between the Control and CAN groups. Leydig cell counts in the testis were comparable between the two groups. The ratios of gene expression for ACEs to that for ACE (ACE2/ACE) in both, the testis and the kidney of the CAN group were significantly lower than those in the Control group, while ACE2/ACE in the lung of the two groups were similar.These results demonstrate that CAN ingestion does not affect gonadotropin secretion from the pituitary while suppresses the testicular function without pathomorphological changes nor Leydig cell count. The decreased ACE2/ACE in the testis and the kidney of the CAN group may affect the local renin-angiotensin-aldosterone system (RAAS). In this presentation the relationship among testosterone, aldosterone and RAAS in the CAN toxicity is discussed.

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